Table 2.

Genes to Consider in the Differential Diagnosis of NTHL1 Tumor Syndrome

MOIGene(s) 1DiffDx DisorderClinical Features of DiffDx Disorder
Overlapping w/NTHL1 tumor syndromeDistinguishing from NTHL1 tumor syndrome
AR MSH3 Familial adenomatous polyposis 4 (OMIM 617100)
  • ↑ CRC risk
  • 10-100 adenomas
  • Duodenal adenomas
No other cancer risk reported
MUTYH MUTYH polyposis
  • ↑ CRC risk
  • Usually 10-100 adenomas
  • Serrated polyps also observed
  • Duodenal adenomas
AD APC Attenuated familial adenomatous polyposis
  • ↑ CRC risk
  • Usually 10-100 adenomas
  • Duodenal adenomas
Extracolonic manifestations (e.g., desmoid tumors, fundic gland polyps, congenital hypertrophy of retinal pigmented epithelium, dental abnormalities, fibromas, lipomas, & osteomas)
BMPR1A
SMAD4 		Juvenile polyposis syndrome ↑ CRC risk
  • GI hamartomatous (juvenile) polyps
  • ↑ risk of cancers of upper GI tract & pancreas
  • Hereditary hemorrhagic telangiectasia (SMAD4-related)
EPCAM
MLH1
MSH2
MSH6
PMS2 		Lynch syndrome
  • ↑ CRC risk
  • Endometrial cancer
  • Usually <10 adenomas
  • ↑ risk for ovarian cancer
  • Sebaceous skin tumors
  • Mismatch repair deficient tumors
Duplication upstream of GREM1Hereditary mixed polyposis syndrome (OMIM 601228)
  • Adenomatous polyps
  • ↑ CRC risk
Mixed polyposis (hyperplastic, atypical juvenile & adenomatous polyps)
POLD1 CRC, susceptibility to, 10 (OMIM 612591)
  • 10-100 adenomas
  • ↑ CRC & endometrial cancer risk
Astrocytoma risk
POLE CRC, susceptibility to, 12 (OMIM 615083)
  • 10-100 adenomas
  • ↑ CRC, ureter, & endometrial cancer
↑ risk for ovarian, gastric cancer, & astrocytoma
PTEN PTEN hamartoma tumor syndrome ↑ CRC, breast, & endometrial cancer risk
  • Multiple hamartomatous & mixed polyps in GI tract
  • Macrocephaly, lipomas of the skin & multinodular goiter
  • ↑ risks for melanoma, thyroid, & renal cancers
STK11 Peutz-Jeghers syndrome ↑ CRC & breast cancer risk
  • GI hamartomatous polyps, most often in small bowel
  • Typical mucocutaneous pigmentation
  • ↑ risk for lung, gastric, pancreas, & sex organ cancers
TP53 Li-Fraumeni syndrome ↑ CRC & breast cancer risk↑ risk for sarcoma, lung cancer, adrenocortical carcinoma, choroid plexus carcinoma, & additional cancers

AD = autosomal dominant; AR = autosomal recessive; DiffDx = differential diagnosis; GI = gastrointestinal; MOI = mode of inheritance; CRC = colorectal cancer

1.

Listed by mode of inheritance, then alphabetically by gene

From: NTHL1 Tumor Syndrome

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